Phenylketonuria: contemporary screening and diagnosis

Screening newborns for phenylketonuria (PKU) is a mandatory practice based on measuring a raised blood phenylalanine level. Many factors influence the rate of blood phenylalanine rise so that there are many pitfalls in detecting the 1:10,000 affected infant. About one percent of all babies tested proves to be "false positives." Two-thirds of those with persistent hyperphenylalaninemia prove to have classic PKU. Non-classic PKU with less intense, persistent hyperphenylalaninemia is due to different alterations in the enzyme, phenylalanine hydroxylase. Additionally, about one percent of the confirmed positive patients is due to either a defect in the synthesis or regeneration of the cofactor, tetrahydrobiopterin; these latter forms are not amenable to treatment with the low phenylalanine diet. Screening programs have developed directives regarding the timing and conditions for obtaining the specimens for testing. Specific confirmatory tests of those with positive results must be performed. Even so, about one in 70 affected babies is "missed," resulting in mental retardation, seizures, and neurologic deficits.